Dipartimento di Chimica Analitica, Università degli Studi di Torino, Via Pietro Giuria 5, 10125 Turin, Italy.
Anal Bioanal Chem. 2011 Oct;401(7):2153-64. doi: 10.1007/s00216-011-5314-7. Epub 2011 Sep 4.
An important goal of forensic and clinical toxicology is to identify biological markers of ethanol consumption that allow an objective diagnosis of chronic alcohol misuse. Blood and head hair samples were collected from 175 subjects-objectively classified as non-drinkers (N=65), social drinkers (N=51) and active heavy drinkers (N=59)-and analyzed to determine eight traditional indirect biomarkers of ethanol consumption [aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), mean corpuscular volume (MCV), carbohydrate-deficient transferrin (CDT), and cholesterol and triglycerides in blood] and one direct biomarker [ethyl glucuronide (EtG) in head hair]. The experimental values obtained from these determinations were submitted to statistical evaluations. In particular, Kruskal-Wallis, Mann-Whitney and ROC curve analyses, together with principal component analysis (PCA), allowed the diagnostic performances of the various biomarkers to be evaluated and compared consistently. From these evaluations, it was possible to deduce that EtG measured in head hair is the only biomarker that can conclusively discriminate active heavy drinkers from social and non-drinkers, using a cut-off value of 30 pg/mg. In contrast, a few indirect biomarkers such as ALP, cholesterol, and triglycerides showed extremely low diagnostic abilities and may convey misleading information. AST and ALT proved to be highly correlated and exhibited quite low sensitivity and specificity. Consequently, either of these parameters can be discarded without compromising the classification efficiency. Among the indirect biomarkers, γ-GT provided the highest diagnostic accuracy, while CDT and MCV yielded high specificity but low sensitivity. It was therefore concluded that EtG in head hair is the only biomarker capable of supporting a confirmatory diagnosis of chronic alcohol abuse in both forensic and clinical practice, while it was found that γ-GT, CDT, MCV, and AST--whether used alone or in combination--do not allow the conclusive classification of subjects according to ethanol consumption. However, a diagnostic strategy combining these four parameters could be formulated in order to create a multivariate model capable of screening suspected active heavy drinkers.
法医毒理学和临床毒理学的一个重要目标是确定乙醇消耗的生物标志物，以客观诊断慢性酒精滥用。从 175 名受试者中采集了血液和头发生长样本-客观地分为非饮酒者（N=65），社交饮酒者（N=51）和活跃的重度饮酒者（N=59）-并进行了分析，以确定八项传统的间接乙醇消耗生物标志物[天冬氨酸氨基转移酶（AST），丙氨酸氨基转移酶（ALT），γ-谷氨酰转移酶（γ-GT），碱性磷酸酶（ALP），平均红细胞体积（MCV），糖缺乏转铁蛋白（CDT）以及血液中的胆固醇和甘油三酯]和一种直接生物标志物[头发生长中的乙基葡糖苷酸（EtG）]。这些测定的实验值经过统计评估。特别是，Kruskal-Wallis，Mann-Whitney 和 ROC 曲线分析以及主成分分析（PCA）允许一致地评估和比较各种生物标志物的诊断性能。从这些评估中，可以推断出，使用 30pg/mg 的截止值，在头发生长中测量的 EtG 是唯一可以明确区分活跃的重度饮酒者，社交饮酒者和非饮酒者的生物标志物。相比之下，少数间接生物标志物（如 ALP，胆固醇和甘油三酯）表现出极低的诊断能力，可能会传递误导性信息。AST 和 ALT 被证明高度相关，并且表现出相当低的灵敏度和特异性。因此，在不影响分类效率的情况下，可以丢弃这些参数中的任何一个。在间接生物标志物中，γ-GT 提供了最高的诊断准确性，而 CDT 和 MCV 具有高特异性但灵敏度低。因此，结论是，头发生长中的 EtG 是唯一能够支持在法医和临床实践中对慢性酒精滥用进行确认诊断的生物标志物，而发现γ-GT，CDT，MCV 和 AST-无论是单独使用还是组合使用-都无法根据乙醇消耗对受试者进行明确分类。但是，可以制定一种包含这四个参数的诊断策略，以创建一个能够筛选可疑的活跃重度饮酒者的多变量模型。
